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dc.contributor.authorBoukalova, Stepana
dc.contributor.authorStursa, Jan
dc.contributor.authorWerner, Lukas
dc.contributor.authorEzrova, Zuzana
dc.contributor.authorCerny, Jiri
dc.contributor.authorBezawork-Geleta, Ayenachew
dc.contributor.authorPecinova, Alena
dc.contributor.authorDong, Lanfeng
dc.contributor.authorDrahota, Zdenek
dc.contributor.authorNeuzil, Jiri
dc.date.accessioned2018-01-23T23:50:31Z
dc.date.available2018-01-23T23:50:31Z
dc.date.issued2016
dc.identifier.issn1535-7163
dc.identifier.doi10.1158/1535-7163.MCT-15-1021
dc.identifier.urihttp://hdl.handle.net/10072/100698
dc.description.abstractPancreatic cancer is one of the hardest-to-treat types of neoplastic diseases. Metformin, a widely prescribed drug against type 2 diabetes mellitus, is being trialed as an agent against pancreatic cancer, although its efficacy is low. With the idea of delivering metformin to its molecular target, the mitochondrial complex I (CI), we tagged the agent with the mitochondrial vector, triphenylphosphonium group. Mitochondrially targeted metformin (MitoMet) was found to kill a panel of pancreatic cancer cells three to four orders of magnitude more efficiently than found for the parental compound. Respiration assessment documented CI as the molecular target for MitoMet, which was corroborated by molecular modeling. MitoMet also efficiently suppressed pancreatic tumors in three mouse models. We propose that the novel mitochondrially targeted agent is clinically highly intriguing, and it has a potential to greatly improve the bleak prospects of patients with pancreatic cancer.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research
dc.relation.ispartofpagefrom2875
dc.relation.ispartofpageto2886
dc.relation.ispartofissue12
dc.relation.ispartofjournalMolecular Cancer Therapeutics
dc.relation.ispartofvolume15
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchOncology and carcinogenesis not elsewhere classified
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321199
dc.subject.fieldofresearchcode3214
dc.titleMitochondrial Targeting of Metformin Enhances Its Activity against Pancreatic Cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorNeuzil, Jiri


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